a study of immunotherapy with til (tumor infiltrating lymphocytes) in combination with intra-tumoral injections of interferon gamma-adenovirus (ad-ifng) in patients with stage iiic or stage iv metastatic melanoma (ajcc)(protocol til-ad-infg)

Conditions: Metastatic Melanoma

Summary: the main objective of this study is to evaluate the clinical and biologic toxicity of cell therapy by adoptive transfer of til in combination with intra-tumoral injections of ad-infg.


Eligibility criteria:
pre-inclusion criteria: * male or female patients ≥ 18 and ≤ 75 years of age * patients must have signed informed consent * a negative pregnancy test for women with childbearing potential * patients with stage iiic/iv metastatic melanoma (ajcc 6th edition) with nodal relapse, in transit metastasis, unresectable cutaneous metastases, visceral metastases except bone and brain metastases * presence of at least one lesion accessible for intra-tumoral injections of ad-ifng * a negative brain scan, eliminating any brain metastases * ecog performance status of 0-2 * adequate bone-marrow reserve, renal function and hepatic function as assessed by standard laboratory criteria * subjects affiliated to an appropriate social security system inclusion criteria: * negative viral serology (hiv ½, p24 ag, htlv 1 / 2, b and c hepatitis) exclusion criteria: * for female : the patient is pregnant or lactating or not using contraception and proved by a negative pregnancy test * positive viral serology for hiv ½, p24 ag, htlv 1 / 2 or b and c hepatitis * history or current manifestations of severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, serious rhythm disorders or ecg signs of previous myocardial infarction) * any serious illness, acute or chronic, e.g. active infection requiring antibiotics, bleeding disorders or any other condition that requires concomitant medications not allowed during this study * presence of a second active cancer except in situ cervical cancer or skin carcinoma * intercurrent disease requiring a corticosteroid treatment or a treatment with interferon-α * any autoimmune disease including active diabetes mellitus or immunodeficiency. vitiligo in not an exclusion criteria * uncontrolled thyroid dysfunction * concurrently participation in a biomedical research (drug or radiotherapy) within the month preceding inclusion * metastatic lymph node stage alone with an indication of lymphadenectomy * brain or bone metastases discovered by radiological examination during the inclusion assessment * surgically resectable metastases * ocular melanoma * more than one line of chemotherapy for treatment of melanoma * chemotherapy, immunotherapy or radiotherapy within 4 weeks before baseline (6 weeks for nitroso-ureas and mitomycin c) * contraindication for the use of vasopressor agents * treatment with molecules in pre-marketing development or whose development is finished less than 4 weeks

Keywords: immunotherapy til (tumor infiltrating lymphocytes) intra-tumoral injection interferon gamma-adenovirus(ad-ifng) metastatic melanoma a stage iiic/iv metastatic melanoma with nodal relapse in transit metastasis cutaneous unresectable metastases visceral metastases